Oat cell carcinoma of the lung requires aggressive combination chemotherapy. Two sequential studies at the BCRP used a combination of cyclophosphamide, doxorubicin and VP16-213 as the basic regimen. The first study showed that MER offered no benefit and the second study showed that alternating chemotherapy did not improve response or survival. The third study tests if increasing the dose and infusion time of VP16-213 can improve response and survival. The overall response rate in the two studies has been identical with 90% total and 60% complete remission (CR) rate in limited disease. Median duration of survival was 9 1/2 and 16 mos for patients with extensive and limited disease, respectively. Patients with limited disease have a 20 to 30% long term disease free survival. Toxicities were managed by dose modification. With the long term survivors, complications of treatment, long term sequelae, and newer disease evolutions have become evident. Leptomeningeal carcinomatosis has been seen in 10 to 15% of patients particularly those with extensive disease and with recurrent disease. Further analyses of these factors is underway.